An apparatus for coaptation of first and second severed nerve segments. The apparatus includes a plurality of nerve-engaging features or coupling members that each connect to another coupling member to form coupling pairs. The coupling pairs are advantageously movable relative to each other to permit nerve swelling, inhibit nerve compression, and facilitate delivery of pharmaceutical agents.
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13. An apparatus for coaptation of a first nerve segment separated from a second nerve segment, comprising:
a first coaptation member configured to extend about the first nerve segment and including a first coupling member configured to engage the first nerve segment, the first coupling member including first epineurium pin configured to pierce the epnieuirum of the first nerve segment; and
a second coaptation member configured to extend about the second nerve segment and including a second coupling member configured to engage the second nerve segment and connected to the first coupling member to inhibit the first and second coaptation members from moving apart in a longitudinal direction and to inhibit the first and second nerve segments from moving apart in the longitudinal direction, the second coupling member including a second epineurium pin configured to pierce the epineurium of the second nerve agent,
wherein (i) the first coupling member and the second coupling member are movable in a transverse direction substantially perpendicular to the longitudinal direction to inhibit nerve compression and (ii) the first coaptation member detachably supports the first epineurium pin, and the second coaptation member detachably supports the second epineurium pin.
7. An apparatus for coaptation of a first nerve segment separated from a second nerve segment, comprising:
a first coupling pair including a first coupling member configured to connect to the first nerve segment and a second coupling member configured to connected to the second nerve segment, and the first coupling member connecting to the second coupling member to engage the first nerve segment with the second nerve segment;
a second coupling pair including a third coupling member configured to connect to the first nerve segment and a fourth coupling member configured to connected to the second nerve segment, and the third coupling member connecting to the fourth coupling member to engage the first nerve segment with the second nerve segment;
a first cylinder-shaped deployment member releasably supporting the first coupling member and the third coupling member and configured to surround the first nerve segment, the first cylinder-shaped deployment member including (i) an inlet passageway configured to deliver a pharmaceutical agent to the first nerve segment and the second nerve segment, and (ii) an outlet passageway configured to evacuate the pharmaceutical agent; and
a second cylinder-shaped deployment member releasably supporting the second coupling member and the fourth coupling member and configured to surround the second nerve segment,
wherein the first coupling pair is movable relative to the second coupling pair to inhibit compression of the first nerve segment and the second nerve segment.
3. An apparatus for coaptation of a first nerve segment separated from a second nerve segment, comprising:
a first coaptation member configured to extend about the first nerve segment and including (i) a first coupling member configured to engage the first nerve segment, the first coupling member including a first epineurium pin configured to pierce the epineurium of the first nerve segment and (ii) a first connection element configured to be disposed apart from the first nerve segment; and
a second coaptation member configured to extend about the second nerve segment and including (i) a second coupling member configured to engage the second nerve segment, the second coupling member including a second epineurium pin configured to pierce the epineurium of the second nerve segment, and connected to the first coupling member to inhibit the first and second coaptation members from moving apart in a longitudinal direction and to inhibit the first and second nerve segments from moving apart in the longitudinal direction, and (ii) a second connection element configured to be disposed apart from the second nerve segment, the second connection element engaging the first connection element to connect the first coaptation member to the second coaptation member;
wherein (i) the first coupling member and the second coupling member are movable in a transverse direction substantially perpendicular to the longitudinal direction to inhibit nerve compression, and (ii) the first coaptation member detachably supports the first epineurium pin and the second coaptation member detachably supports the second epineurium pin.
12. An apparatus for coaptation of a first nerve segment separated from a second nerve segment, comprising:
a first coaptation member configured to extend about the first nerve segment and engage the first nerve segment, the first coaptation member including a first connection element configured to be disposed apart from the first nerve segment; and
a second coaptation member configured to connect to the first coaptation member and configured to extend about the second nerve segment, the second coaptation member including
(i) a first coupling member and a second coupling member each configured to engage the second nerve segment to inhibit the second nerve segment from moving away from the first nerve segment in a longitudinal direction, and the first coupling member and the second coupling member being movable relative to each other in a transverse direction substantially perpendicular to the longitudinal direction to inhibit nerve compression, the first coupling member including a first epineurium pin extending substantially in the longitudinal direction and configured to pierce the epineurium of the second nerve segment, the second coupling member including a second epineurium pin extending substantially in the longitudinal direction and configured to pierce the epineurium of the second nerve segment, and
(ii) a second connection element configured to be disposed apart from the second nerve segment and engaging the first connection element to connect the second coaptation member to the first coaptation member, the first and second connection elements inhibiting movement of the first and second coaptation members and first and second nerve segments apart from each other in the longitudinal direction,
wherein the first coaptation member detachably supports the first epineurium pin, and the second coaptation member detachably supports the second epineurium pin.
1. An apparatus for coaptation of a first nerve segment separated from a second nerve segment, comprising:
a first coaptation member configured to extend about the first nerve segment and engage the first nerve segment, the first coaptation member including (i) a first connection element configured to be disposed apart from the first nerve segment (ii) an inlet passageway configured to deliver a pharmaceutical agent to the first nerve segment and the second nerve segment, and (iii) an outlet passageway configured to evacuate the pharmaceutical agent; and
a second coaptation member configured to connect to the first coaptation member and configured to extend about the second nerve segment, the second coaptation member including (i) a first coupling member and a second coupling member each configured to engage the second nerve segment to inhibit the second nerve segment from moving away from the first nerve segment in a longitudinal direction, and (ii) a second connection element configured to be disposed apart from the second nerve segment and engaging the first connection element to connect the second coaptation member to the first coaptation member, the first coupling member and the second coupling member being movable relative to each other in a transverse direction substantially perpendicular to the longitudinal direction to inhibit nerve compression, and
wherein (i) the first and second connection elements inhibit movement of the first and second coaptation members and first and second never segments apart from each other in the longitudinal direction, (ii) the first coupling member includes a first epineurium pin extending substantially in the longitudinal direction and configured to pierce the epineurium of the second nerve segment, and the second coupling member includes a second epineurium pin extending substantially in the longitudinal direction and configured to pierce the epineurium of the second nerve segment, and (iii) the first coaptation member detachably supports the first epineurium pin, and the second coaptation member detachably supports the second epineurium pin.
2. The apparatus of
4. The apparatus of
5. The apparatus of
6. The apparatus of
an inlet passageway configured to deliver a pharmaceutical agent to the first nerve segment and the second nerve segment; and
an outlet passageway configured to evacuate the pharmaceutical agent.
8. The apparatus of
9. The apparatus of
10. The apparatus of
a plurality of connection posts;
a first plurality of epineurium pins configured to pierce the epineurium of the first nerve segment;
and wherein the second cylinder-shaped member includes:
a plurality of connections holes configured to receive the connection posts and thereby connect the first and second cylinder-shaped members; and
a second plurality of epineurium pins configured to pierce the epineurium of the second nerve segment.
11. The apparatus of
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This application represents the national stage entry of PCT International Application No. PCT/US2012/026764 filed Feb. 27, 2012, which claims the benefit of U.S. Provisional Patent Application No. 61/578,930 filed Dec. 22, 2011 and U.S. Provisional Patent Application 61/446,803 filed Feb. 25, 2011, the disclosures of which are hereby incorporated by reference in their entirety for all purposes
Not applicable.
The present disclosure generally relates to a nerve coaptation apparatus and, more particularly, to a microsuture-less nerve coaptation apparatus having relatively-movable coupling members to inhibit nerve compression in the event of, for example, nerve swelling.
Microsurgery (that is, surgery aided by use of a microscope) is used in various types of medical procedures that treat relatively small bodily structures, such as coaptation of severed nerves. In this case, the procedure typically involves using a relatively small suture to connect the severed ends of the severed nerve segments. This facilitates axonal growth to fuse the nerve segments, which ideally restores some degree of nerve functionality.
Unfortunately, nerve coaptation microsutures have several limitations. For example, connecting severed nerve segments with a microsuture is a relatively long procedure that requires considerable surgical experience. Furthermore, the outcome of such procedures are typically considered poor due to relatively long recovery times (for example, up to several years) and limited nerve functionality (for example, less than 20 percent of original nerve functionality).
Nerve coaptation couplings have been proposed for use in addition to microsutures in an attempt to address the above limitations. Such couplings typically include a sleeve that houses and isolates the ends of the severed nerve segments, and pharmaceutical agents can be incorporated into the sleeve to promote axonal growth. Unfortunately, such devices inhibit nerve swelling proximate the ends of the severed nerve segments, which inwardly compresses the nerve segments and can adversely affect nerve regeneration.
Considering the above, what is needed is a nerve coaptation apparatus that addresses one or more of the shortcomings of microsutures and previous coaptation devices.
The present invention generally provides an apparatus for coaptation of first and second severed nerve segments. The apparatus includes a plurality of nerve-engaging features or “coupling members” that each connect to another coupling member to form “coupling pairs”. The coupling pairs are advantageously movable relative to each other to permit nerve swelling and inhibit nerve compression.
In one aspect, the present invention provides an apparatus for coaptation of a first nerve segment separated from a second nerve segment. The apparatus includes a first coaptation member configured to extend about the first nerve segment and engage the first nerve segment. The apparatus further includes a second coaptation member configured to connect to the first coaptation member and extend about the second nerve segment. The second coaptation member includes a first coupling member and a second coupling member that are each configured to engage the second nerve segment to inhibit the second nerve segment from moving away from the first nerve segment in a longitudinal direction. The first coupling member and the second coupling member are movable relative to each other in a transverse direction substantially perpendicular to the longitudinal direction to inhibit nerve compression.
In another aspect, the present invention provides an apparatus for coaptation of a first nerve segment separated from a second nerve segment. The apparatus includes a first coaptation member configured to extend about the first nerve segment, and the first coaptation member includes a first coupling member configured to engage the first nerve segment. The apparatus further includes a second coaptation member configured to extend about the second nerve segment, and the second coaptation member includes a second coupling member configured to engage the second nerve segment. The second coupling member connects to the first coupling member to inhibit the first and second coaptation members from moving apart in a longitudinal direction and to inhibit the first and second nerve segments from moving apart in the longitudinal direction. The first coupling member and the second coupling member are movable in a transverse direction substantially perpendicular to the longitudinal direction to inhibit nerve compression.
In yet another aspect, the present invention provides an apparatus for coaptation of a first nerve segment separated from a second nerve segment. The apparatus includes a first coupling pair having a first coupling member configured to connect to the first nerve segment and a second coupling member configured to connected to the second nerve segment. The first coupling member connects to the second coupling member to engage the first nerve segment with the second nerve segment. The apparatus further includes a second coupling pair having a third coupling member configured to connect to the first nerve segment and a fourth coupling member configured to connected to the second nerve segment. The third coupling member connects to the fourth coupling member to engage the first nerve segment with the second nerve segment. The first coupling pair is movable relative to the second coupling pair to inhibit compression of the first nerve segment and the second nerve segment.
The foregoing and other objects and advantages of the invention will appear in the detailed description that follows. In the description, reference is made to the accompanying drawings that illustrate a preferred configuration of the invention.
The present invention will hereafter be described with reference to the accompanying drawings, wherein like reference numerals denote like elements, and:
Referring now to
The coaptation members 52, 54 also receive one or more pharmaceutical agents from an agent delivery device 56 to facilitate repair and fusion of the nerve segments 10, 12. Various pharmaceutical agents may be used, although advantageous pharmaceutical agents are described below. Regardless of the specific type used, the pharmaceutical agents are subsequently evacuated to a collection device 58.
Turning now to
The first coaptation member 102 includes a plurality of coupling members 106, which may comprise various materials commonly associated with medical devices, such as implantable, biodegradable, and non-neurotoxic polymers and the like. Each of the coupling members 106 includes a semi-cylindrical wall 108, and together the walls 108 provide the first coaptation member 102 with a cylindrical shape for receiving the first nerve segment 10. That is, the coupling members 106 together define open ends 110, 112 through which the nerve segment 10 extends and an internal nerve passageway 114 that receives nerve segment 10. Furthermore, the coupling members 106 together define a longitudinal direction of the coaptation member 102 extending between the open ends 110, 112 and aligned with the longitudinal direction of the nerve segment 10.
To permit the coupling members 106 to move relative to each other, the first coaptation member 102 includes a plurality of expandable or flexible joints 116 connecting the sides of adjacent coupling members 106. The flexible joints 116 may comprise various materials, such as elastically deformable, implantable, biodegradable, and non-neurotoxic polymers and the like. In any case, the flexible joints 116 permit the coupling members 106 to move in a transverse direction (that is, a direction perpendicular to the longitudinal direction within five degrees) relative to one another. Such relative motion between the coupling members 106 advantageously permits nerve swelling (by up to, for example, 50 percent) and inhibits nerve compression.
The first coaptation member 102 includes several features to engage the first nerve segment 10 and the second coaptation member 104 proximate the open end 110. To connect to the nerve segment 10, each of the coupling members 106 includes a hooked epineurium pin 118. As the name implies, each epineurium pin 118 pierces the epineurium of the nerve segment 10. As such, the epineurium pins 118 inhibit the nerve segment 10 from moving longitudinally relative to the coaptation member 102. In addition, the epineurium pins 118 hold the nerve segment 10 in an appropriate position for coaptation with the second nerve segment 12 (that is, proximate the open end 110) when the coaptation members 102, 104 are connected.
To connect the first coaptation member 102 to the second coaptation member 104, each of the coupling members 106 includes two longitudinally extending connection elements 120, 122 proximate the first open end 110. Half of the connection elements are tapering posts 120 and half of the connection elements are holes 122. Each hole 122 receives one of the tapering posts 120 on the second coaptation member 104, and each tapering post 120 is received in one of the holes 122 on the second coaptation member 104. In addition, each tapering post 120 may be press-fittingly received in the corresponding hole 122 to provide a firm connection between the coaptation members 102, 104. Such a connection may inhibit the coaptation members 102, 104 from moving apart in the longitudinal direction once connected.
One or more of the coupling members 106 also include features to ensure proper angular alignment of the nerve segments 10, 12 (that is, proper alignment of individual axons and the like). Specifically, on each of the coaptation members 102, 104, one of the coupling members 106 includes a plurality of strips 124, 126, and 128 of different colors. When connecting the nerve segments 10, 12 to the coaptation members 102, 104, respectively, common features of the nerve segments 10, 12 (for example, fascicle patterns or the like) may be aligned with a specific strip 124, 126, or 128. Then, when connecting the coaptation members 102, 104 to each other, matching color strips 124, 126, and 128 on the coaptation members 102, 104 are aligned to ensure that the features of the nerve segments 10, 12 are aligned. Furthermore, the coupling members 106 could be translucent or transparent to permit the nerve segments 10, 12 to be viewed therethrough.
During deployment, the coaptation members 102, 104 may be moved towards each other and joined using a linear or hinged coupling applicator, such as those used for vascular anastomoses. Other deployment devices may alternatively be used.
After deployment, one or more pharmaceutical agents may be delivered from the agent delivery device, through an inlet passageway 130 defined by one of the coupling members 106, and into the nerve passageways 114 to facilitate repair and fusion of the nerve segments 10, 12. After a specified amount of time, the pharmaceutical agents are evacuated through an outlet passageway 132 defined by one of the coupling members 106 and into the collection device.
The first configuration of the nerve coaptation apparatus 100 may be modified in other manners that are not explicitly described above. For example, the coupling members 106 may include more or less than two connection elements 120, 122 and one epineurium pin 118 (for example, each coaptation member 102 and 104 may include twelve connection elements 120, 122 and six epineurium pins 118). As another example, the inlet passageway 130 and outlet passageway 132 may be omitted, and gaps defined by the flexible joints 116 and the sides of adjacent coupling members 106 may serve as inlet and outlet passageways.
Turning now to
The first coaptation member 202 may comprise various materials commonly associated with medical devices, such as non-neurotoxic polymers and the like. The first coaptation member 202 includes a wall 206 that defines a cylindrical shape for receiving the first nerve segment 10. That is, the wall 206 defines open ends 208, 210 through which the nerve segment 10 extends and an internal nerve passageway 212 that receives nerve segment 10. Furthermore, the coaptation member 202 defines a longitudinal direction extending between the open ends 208, 210 and aligned with the longitudinal direction of the nerve segment 10.
The first coaptation member 202 also supports connection elements 214, 216, such as those described above, to connect to the second coaptation member 204. That is, the coaptation member 202 includes a plurality of longitudinally extending connection elements 214, 216 proximate the first open end 208. Half of the connection elements are tapering posts 214 and half of the connection elements are holes 216. Each hole 216 receives one of the tapering posts 214 on the second coaptation member 204, and each tapering post 214 is received in one of the holes 216 on the second coaptation member 204. In addition, each tapering post 214 may be press-fittingly received in the corresponding hole 216 to provide a firm connection between the coaptation members 202, 204. Such a connection may inhibit the coaptation members 202, 204 from moving apart in the longitudinal direction once connected.
The first coaptation member 202 also includes inlet and outlet passageways 218, 220 to receive and evacuate one or more pharmaceutical agents, respectively. In this configuration, the inlet and outlet passageways 218, 220 are defined adjacent to bridges 222 that connect opposite semi-cylindrical halves 224 of the coaptation member 202.
As described briefly above, the first coaptation member 202 releasably supports a plurality of coupling members 226, 228 on the inner surface of the wall 206. The coupling members 226, 228 engage and hold the first nerve segment 10 in contact with the second nerve segment 12. As such, the coupling members 226, 228 may comprise various materials commonly associated with medical devices, such as implantable, biodegradable, and non-neurotoxic polymers and the like.
To engage and hold the first nerve segment 10 in contact with the second nerve segment 12, half of the coupling members 226 have tapering shapes and act as epineurium pins that pierce the epineurium of the nerve segment 10. In addition, these coupling members 226 are fixedly received by a corresponding pin-receiving coupling member 228 of the second coaptation member 204. Similarly, each pin-receiving coupling member 228 of the first coaptation member 202 fixedly receives one of the epineurium pin coupling members 226 of the second coaptation member 204.
After receiving the nerve segments 10, 12, connecting to each other, and delivering and evacuating the pharmaceutical agents, the coaptation members 202, 204 detach from the coupling members 226, 228, for example, by breaking the bridges 222 and an adhesive connection between the coaptation members 202, 204 and the coupling members 226, 228. The coupling members 226, 228 remain connected to each other and the nerve segments 10, 12. As such, the coupling members 226, 228 inhibit the nerve segments 10, 12 from moving apart in the longitudinal direction. However, each pair of coupling members 226, 228 is movable in the transverse direction relative to the other pairs. The coupling members 226, 228 thereby permit nerve swelling and inhibit compression.
Turning now to
In contrast to the second configuration, each coaptation member 302, 304 includes two separate semi-cylindrical halves 318 that are initially held in abutment by a semi-cylindrical deployment element 320. As such, after connecting the nerve segments 10, 12 to the coupling members 310, 312 and connecting the coaptation members 302, 304 to each other, the deployment elements 320 are detached from the coaptation members 302, 304 by, for example, moving the deployment elements 320 apart in the longitudinal direction. Thereafter, and as shown in
For each of the above configurations, the coaptation members may provide a range of sizes appropriate for use with digital nerve repair (about 1 mm in diameter) up to brachial root repair (about 1 cm in diameter).
Turning now to
Regardless of the specific type of agent delivery device, the pharmaceutical agents preferably and advantageously include a sequence of: 1) a hypotonic calcium-free solution (for example, a solution as shown below in Tables 1 and 2 applied for a period of about 60 seconds before evacuation); 2) antioxidants/inhibitors of membrane sealing (for example, 2 mM melatonin or 100 μM USP methylene blue applied for a period of about 90 seconds before evacuation); 3) a lipid membrane fusogen (for example, 5 g polyethylene glycol 2000 (PEG) dissolved in 5 mL distilled water applied for about 90 seconds before evacuation); and; 4) isotonic calcium-containing solution (for example, a solution as shown below in Tables 3-5 applied for a period of about 120-180 seconds before evacuation).
TABLE 1
Hypotonic calcium-free solution. Chemicals dissolved in 1000 mL distilled
water, buffering pH with HCl or NaOH, respectively, added drop-wise.
Symbol
Chemical
Amount
MW
Factor
mM/L
Species
mOsm/L
NaCl
Sodium Chloride
5.7856
g
58.44
1
99
2
198
KCl
Potassium Chloride
0.3728
g
74.56
1
5
2
10.0
KH2PO4
Potassium Phosphate
0.1634
g
136.09
1
1.2
2
2.4
MgSO4
Magnesium Sulfate
0.1566
g
120.39
1
1.3
2
2.6
NaHCO3
Sodium Bicarbonate
2.1842
g
84.01
1
25
2
50.0
NaC6H7o6
Sodium Ascorbate
1.981
g
198.1
1
10
2
20.0
C6H12O6
Dextrose
1.8
g
180.16
1
9.9
1
10.0
—
Solution A
50
mL
95.21
85.49/10
8.55
3
25.7
(see Table 2)
273.7
318.7
TABLE 2
Solution A. Dissolved in 500 mL distilled water.
Symbol
Chemical
Amount (g)
MW
Multiplicand
mM/L
Species
mOsm/L
MgCl2
Magnesium
4.07
95.21
2
85.49
3
256.47
Chloride
TABLE 3
Isotonic calcium-containing solution. Buffer pH with
HCl or NaOH, respectively, added drop-wise. Mix cold.
Symbol
Chemical
Amount
MW
mM/L
Species
mOsm/L
—
Solution B
475
mL
473.49
331.55
1
314.97
(see Table 4)
H2O
Distilled
475
mL
18
—
—
Water
—
Solution C
50
mL
111.0
2
3
6.0
(see Table 5)
NaC6H7o6
Sodium
1.981
g
198.1
10
2
20
Ascorbate
C6H12O6
Dextrose
1.8
g
180.16
9.9
1
9.9
350.87
TABLE 4
Solution B. Chemicals dissolved in 4000 mL distilled water.
Symbol
Chemical
Amount (g)
MW
Divisor
mM/L
Species
mOsm/L
NaCl
Sodium Chloride
61.024
58.44
4
261.05
2
522.1
KCl
Potassium Chloride
3.139
74.56
4
10.5
2
21
KH2PO4
Potassium Phosphate
1.374
136.09
4
2.52
2
5.04
MgSO4
Magnesium Sulfate
1.318
120.39
4
2.74
2
5.48
NaHCO3
Sodium Bicarbonate
18.394
84.01
4
54.74
2
109.48
473.49
331.55
663.1
TABLE 5
Solution C. Dissolved in 1000 mL distilled water.
Symbol
Chemical
Amount (g)
MW
mM/L
Species
mOsm/L
CaCl2
Calcium
4.44
111.0
40
3
120
Chloride
Alternatively, the hypotonic calcium-free solution may be additionally applied to the nerve after the antioxidants/inhibitors of membrane sealing and before the lipid membrane fusogen to wash away USP methylene blue stains on the nerve segments.
Data collected by the present inventors and partially illustrated in
After the specified contact period with the nerve segments, each pharmaceutical agent may be evacuated by applying vacuum pressure, permitting free drainage, capillary action (for example, by connecting the outlet passageway to an absorbent surgical material), or the like. Furthermore, the actions of the delivery device and the collection device can be coordinated, for example, via an electronic controller (not shown) and a plurality of valves (not shown), such that each pharmaceutical agent contacts the nerve segments for the specified contact period. Such a controller may also control the delivery pressure of the pharmaceutical agents. That is, the controller may provide the agents at a pressure sufficiently low to maintain contact of the ends of the nerve segments, and sufficiently high to ensure adequate distribution of the chemicals over the nerve segments.
The pharmaceutical agent delivery sequence may be summarized as follows.
A method for treatment of a nerve, comprising the steps of:
delivering at least one of an antioxidant and an inhibitor of membrane sealing to the nerve;
evacuating the at least one of the antioxidant and the inhibitor of membrane sealing away from the nerve;
delivering at least one lipid membrane fusogen to the nerve after evacuating the at least one of the antioxidant and the inhibitor of membrane sealing; and
evacuating the at least one lipid membrane fusogen away from the nerve.
In some configurations, the at least one of the antioxidant and the inhibitor of membrane sealing includes one of USP methylene blue and melatonin.
In some configurations, the at least one lipid membrane fusogen includes polyethylene glycol.
In some configurations, the method further comprises the steps of:
delivering at least one hypotonic calcium-free solution to the nerve; and
evacuating the at least one hypotonic calcium-free solution away from the nerve before delivering the at least one of the antioxidant and the inhibitor of membrane sealing.
In some configurations, the method further comprises the steps of:
delivering at least one isotonic calcium-containing solution to the nerve after evacuating the at least one lipid membrane fusogen; and
evacuating the at least one isotonic calcium-containing solution away from the nerve.
In some configurations, the nerve includes a first segment severed from and abutting a second segment, and each of the at least one of the antioxidant and the inhibitor of membrane sealing and the at least one lipid membrane fusogen are delivered to and evacuated away from the first segment and the second segment.
The pharmaceutical agents may be provided in a kit. Such a kit may be summarized as follows.
A kit for use in a pharmaceutical agent delivery sequence, comprising:
at least one of an antioxidant and an inhibitor of membrane sealing;
at least one lipid membrane fusogen; and
instructions indicating that the pharmaceutical agent delivery sequence includes at least one of the antioxidant and the inhibitor of membrane sealing followed by the at least one lipid membrane fusogen.
From the above description, it should be apparent that the present invention provides a nerve coaptation apparatus that includes a plurality of nerve-engaging coupling pairs. The coupling pairs are advantageously movable relative to each other to permit nerve swelling and inhibit nerve compression.
The various configurations presented above are merely examples and are in no way meant to limit the scope of this disclosure. Variations of the configurations described herein will be apparent to persons of ordinary skill in the art, such variations being within the intended scope of the present application. In particular, features from one or more of the above-described configurations may be selected to create alternative configurations comprised of a sub-combination of features that may not be explicitly described above. In addition, features from one or more of the above-described configurations may be selected and combined to create alternative configurations comprised of a combination of features which may not be explicitly described above. Features suitable for such combinations and sub-combinations would be readily apparent to persons skilled in the art upon review of the present application as a whole. The subject matter described herein and in the recited claims intends to cover and embrace all suitable changes in technology.
Winograd, Jonathan M., Keating, Cameron P., Omobono, Mark
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